Aldeyra to Resubmit Reproxalap NDA Following Phase 3 Success

Aldeyra Therapeutics has announced that its investigational dry eye disease (DED) candidate, reproxalap, met the primary endpoint in a Phase 3 randomized, double-masked, vehicle-controlled dry eye chamber trial. The company now plans to resubmit its New Drug Application (NDA), potentially addressing previous regulatory concerns outlined by the U.S. Food and Drug Administration (FDA).

In the trial, reproxalap (n=58) demonstrated statistically significant superiority over vehicle (n=58) in ocular discomfort symptom score (0–100 scale) between 80 and 100 minutes after chamber entry. The least squares (LS) mean difference was 6.5 with a 95% confidence interval of [–10.5, –2.5] (P=0.002), supporting a rapid clinical effect.

Addressing FDA Feedback After April 2025 Complete Response Letter

This latest chamber trial follows an April 2025 Complete Response Letter (CRL) from the FDA, which cited concerns about a previous dry eye chamber study, particularly baseline imbalances across treatment arms that may have affected data interpretation.

Aldeyra noted that the new chamber trial did not exhibit notable baseline differences, potentially resolving the FDA’s concerns. A Type A meeting with the FDA is anticipated, and pending this discussion, Aldeyra expects to resubmit the NDA in mid-2025, with a projected 6-month review period.

“The dry eye chamber results announced today are representative of a number of clinical trials that highlight the potential rapid clinical effect of reproxalap on reducing ocular discomfort,” said Todd C. Brady, MD, PhD, President and CEO of Aldeyra.
“With no notable baseline differences across treatment arms and highly statistically significant results in favor of reproxalap over vehicle, we believe the data potentially address the FDA feedback in the Complete Response Letter received last month.”

Additional Supportive Data from Field Study

Alongside the chamber trial, Aldeyra also completed a dry eye disease field trial. Although numerically supportive and consistent with prior results, the study did not reach statistical significance. The company intends to include this dataset in the upcoming NDA resubmission as supportive evidence.

Safety and Tolerability Confirmed Across Studies

Across the two most recent trials, no safety signals or treatment-related discontinuations were reported. Reproxalap continued to demonstrate a favorable tolerability profile, with the most commonly reported adverse event being mild, transient instillation site discomfort. To date, reproxalap has been studied in over 2,900 patients.

A First-in-Class Candidate with Acute and Chronic DED Activity

Aldeyra emphasized that reproxalap may be the first investigational drug for DED with pivotal data supporting both acute and chronic symptom reduction, as well as the first chronic-use therapy with pivotal data demonstrating benefit in acute exacerbation of ocular redness.